N/A
This invention relates generally to mass spectrometry, and in particular to a photoionization source that is coupled to a source of vapor.
The application of mass spectroscopy has emerged from the confines of academic laboratories and has entered the commercial market place. Liquid chromatography/mass spectroscopy (LC/MS) is one of the fastest growing segments of analytical instrumentation primarily due to new applications in biotechnology, including the analysis of biopharmaceuticals. LC/MS requires the ionization of some of the molecules to be analyzed. Some ionization methods impart excess energy to the molecules causing fragmentation, which increases the number of different ions to be analyzed. This greater number of ions increases the number of output signals, which makes it harder to interpret the results of the analysis. The high-energy ionization methods are referred to as hard ionization methods.
Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are two soft ionization methods commonly used for analyzing liquid samples while minimizing fragmentation. These are methods in which the analytes either protonate to form adducts for positive ion mode or deprotonate (or electron attach) for negative ion mode. In addition to ESI and APCI, photoionization and in particular atmospheric photoionization (APPI) is a soft ionization method generally used for analyzing samples from high-flow devices such as the effluent from a liquid chromatograph.
Currently mass spectroscopy systems employing APPI sources have a xe2x80x9cside armxe2x80x9d discharge lamp employing, e.g., Kr, wherein the photons are transmitted through a window that is in close proximity to a quartz tube of a heated nebulizer adapted from those used in an APCI system. In this configuration, the photoionization discharge lamp is mounted to the side of the quartz tube of a heated nebulizer from which the corona discharge needle has been removed. A similar system, which positions the discharge lamp at the back of the APCI source housing, and the heated nebulizer probe, without corona discharge needle, is located at right angles to both the discharge lamp window and the inlet for the mass spectrometer. The above systems often infuse a dopant, usually toluene or acetone, into an auxiliary gas line of the heated nebulizer in order to provide chemical ionization as well as the photoionization. This often limits the applicability and advantages observed with photoionization.
In practice, while these APPI systems have the advantage of operating at atmospheric pressure, they have notable disadvantages. For example, acetonitrile, which is an advantageous mobile phase for HPLC separations cannot be used as a mobile phase for prior art APPI LC/MS applications due to acetonitrile""s absorption of the UV photons in the relatively small photoionization zone. Another disadvantage, caused in part by the distance between the vapor and the lamp, is the inefficiency of the present direct photoionization of the sample molecule methods. This inefficiency promotes the use of dopant additives such as toluene. Addition of a dopant adds considerable complexity to an MS system. In this type of situation, the dopant is typically more easily photoionized than the molecule of interest. After the photoionization of the dopant, the dopant itself reacts with the molecule of interest in a chemical ionization step, thus rendering the ionization process more like chemical ionization than photoionization.
There is currently a need to have a more efficient photoionization source that can be coupled to a heated nebulizer and perform at, or near, atmospheric pressure. It is desirable to have a mass spectroscopy system that uses a larger photoionization interaction zone with the effluent from a nebulizer. Moreover, a greater photon flux is desired to yield a better photoionization efficiency and sensitivity. Further, it is desirable to have an APPI LC/MS system that has sufficient efficiency that it can accommodate UV-absorbing solvents such as the commonly used acetonitrile. Additionally, it is desirable to have an APPI LC/MS system in which dopants are not required for improving efficient ionization of the molecules of interest.
The present invention is directed to photoionization source useful with mass spectrometers. The photoionization source comprises a discharge lamp, preferentially formed in a coaxial manner, that is coupled with a vapor source that is at, or near, atmospheric pressure. The vapor source in one embodiment is a nebulizer that is heated to drive the solvents from the vapor. The various gases utilized with the heated nebulizer, i.e. nebulizer gas and coaxial (sometimes called xe2x80x9cauxiliaryxe2x80x9d) gas, are typically supplied from a single supply line of nitrogen. While other gases like helium or oxygen could be used, they are not preferred due to excess consumption, expense, and the fact that they will absorb the UV radiation, etc. In addition, any solvent vapor has some potential to absorb the radiation.
In one embodiment, a photoionization source comprises a source of vapor of one or more compounds of interest that causes the vapor to travel in a path defining an axis toward an inlet and a lamp for emitting photons into the vapor path. The lamp has a photon emitting region disposed at a radial distance along the axis, where the axis toward the inlet may be distinct from the centerline of the vapor path. The lamp is in communication with the source of vapor such that the photons are emitted into the vapor traveling on the path producing ionization of the compounds. In some embodiments, the lamp is placed adjacent to the vapor source but is not connected to it. In other embodiments, the lamp is connected to the vapor source by a coupler.
In some configurations, the compounds of interest come into the vapor source from an in-line liquid chromatography apparatus. When a nebulizer is used as the vapor source, it may operate at atmospheric pressure. One or more heating elements capable of heating the nebulizer from about ambient temperature to about 800xc2x0 C. may be disposed about the nebulizer. The heated nebulizer produces dryer vapor. The nebulizer has a nebulizer tube that is comprised of material selected from the group consisting of quartz, ceramic, fused silica, glass, and stainless steel.
The lamp in the photoionization source may be a discharge lamp. This lamp may have a photon emitting region that subtends an arc of between 90 and 360 degrees about an axis. The lamp then forms an arched passageway for the vapor being ionized. In one embodiment, the photon emitting region encompasses 360 degrees about the lamp axis forming a tube wherein the vapor receives photons from all angles. The lamp contains one or more noble gases that are capable of emitting photons when excited. The excited gases emit photons having energies on the order of from about 7 eV to about 15 eV. One or more of the lamps of the invention may be clustered, radially or longitudinally, to provide a larger ionization region.
In one embodiment, the discharge lamp comprises an ultra-violet transparent tube surrounded by a discharge lamp envelope, that is sealed to the ultra-violet transparent tube, and an Rf discharge coil that is disposed adjacent and external to the lamp envelope. The lamp envelope contains one or more noble gases that are excited, thereby emitting photons, when the Rf discharge coil provides sufficient electrical energy. The ultra-violet transparent tube comprises material selected from the group consisting of quartz, MgF2, CaF2, and LiF and the lamp envelope is made from material selected from the group consisting of glass, soda glass, borosilicate and quartz. A Rf generator drives the Rf discharge coil.
In one embodiment, the centerline of the vapor path and the axis toward the inlet are approximately aligned allowing most of the vapor to pass through the lamp. In another embodiment, the axis is at an angle with respect to the centerline of the vapor path allowing some vapor to be excluded from the excitation path. The vapor source and lamp may be aligned with some space therebetween or may be connected by a connector.
In one embodiment, a mass spectrometer comprises a nebulizer outputting a vapor of one or more components of interest, a lamp for emitting photons into the vapor and a coupler that facilitates the coupling of the nebulizer to the lamp. The vapor travels in a path that defines an axis through the coupled components toward an inlet. The coupler comprises material selected from the group consisting of glass, fused silica, quartz, ceramic, copper, stainless steel, and combinations thereof. The nebulizer further comprises at least one heating element for heating the nebulizer to temperatures between ambient and 800xc2x0 C. The nebulizer operates at atmospheric pressure.
The lamp has a photon emitting region at a radius along the axis such that photons are emitted into the vapor traveling on the path to produce ionization of the compounds. The photon emitting region is an ultra-violet transparent region. The lamp is charged with one or more noble gases that are capable of emitting photons when excited. In one embodiment, an in-line liquid chromatography apparatus is connected to an input of the nebulizer and the inlet communicates with a mass detector.
In one embodiment, a mass spectrometer comprises an in-line liquid chromatography apparatus connected to a nebulizer operating under atmospheric pressure that outputs a vapor toward a discharge lamp so that the gases in the vapor are excited as they pass through the discharge lamp. The excited gas interacts with a mass detector. The nebulizer may comprise at least one heating element for heating the nebulizer to temperatures between ambient and 800xc2x0 C. In the discharge lamp, the excited gases emit photons on the order of from about 7 eV to about 15 eV. In one embodiment, the discharge lamp is tube shaped and is approximately aligned along a central axis with the nebulizer. In another embodiment, the central axis of the discharge lamp is at an angle with respect to the central axis of the nebulizer.
In one embodiment of the present invention, a mass spectrometer comprises an APPI source that has a coaxial discharge lamp that is in communication with a nebulizer. In one aspect of this embodiment, the discharge lamp is not structurally integrated with the nebulizer, rather it is disposed adjacent to the nebulizer. In one aspect, the discharge lamp and the nebulizer are aligned along a central axis facilitating the flow of a nebulized gas from the nebulizer to the discharge lamp. In another aspect, the discharge lamp is oriented at an angle to the central axis of the nebulizer allowing nebulized material to enter the discharge lamp while incompletely nebulized material is excluded. One or more heating elements, such as a heating coil, are included in the design of the disclosed APPI source. The heating element(s) provides the nebulizer with heat energy in order to attain the nebulization temperatures of up to 800xc2x0 C. In one aspect of the invention, the nebulization temperature is optimally between from about ambient temperature to about 400xc2x0 C. Some compounds will degrade rather than nebulize at higher temperatures, so these lower temperatures are appropriate in such cases. The APPI source of the present invention can be used in combination with an in-line liquid chromatography (LC) apparatus. The effluent from the LC apparatus enters the heated nebulizer, which is under atmospheric pressure. From the heated nebulizer, the effluent proceeds directly into the coaxial discharge lamp region of the APPI source where optimal photoionization occurs. Finally, the ionized sample travels to and is analyzed by a mass detector.
The design of the photoionization source of the instant invention offers significant advantages over the prior art. It produces an increased photon flux, which results in increased photoionization efficiency. Another significant benefit of an increased photon flux is that the effect of absorption of the UV radiation by solvents such as acetonitrile is mitigated. This feature of the present invention permits a practitioner to freely employ commonly used chromatography solvents like acetonitrile in their protocols. Another benefit of the instant invention is that the effluent from a heated nebulizer interacts with a larger photoionization interaction zone. Additionally, a dopant is not necessary in the sample processed by the APPI system of the present invention, however, a dopant could be employed if desired. Moreover, the coaxial design of the photoionization source of the instant invention allows photons from the discharge lamp to penetrate the vapor output from the heated nebulizer from all sides, thus increasing photoionization efficiency. The photoionization source may be placed so that only a portion of the output of the nebulizer enters the source, allowing xe2x80x9cwetxe2x80x9d vapor to be excluded.